Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California.
Department of Radiation Oncology, Centre Hospitalier de l'Université de Montreal, Montreal, Quebec, Canada.
Clin Cancer Res. 2019 Dec 1;25(23):7078-7088. doi: 10.1158/1078-0432.CCR-19-1832. Epub 2019 Aug 16.
Previous studies indicate that the benefit of therapy depends on patients' risk for cancer recurrence relative to noncancer mortality (ω ratio). We sought to test the hypothesis that patients with head and neck cancer (HNC) with a higher ω ratio selectively benefit from intensive therapy.
We analyzed 2,688 patients with stage III-IVB HNC undergoing primary radiotherapy (RT) with or without systemic therapy on three phase III trials (RTOG 9003, RTOG 0129, and RTOG 0522). We used generalized competing event regression to stratify patients according to ω ratio and compared the effectiveness of intensive therapy as a function of predicted ω ratio (i.e., ω score). Intensive therapy was defined as treatment on an experimental arm with altered fractionation and/or multiagent concurrent systemic therapy. A nomogram was developed to predict patients' ω score on the basis of tumor, demographic, and health factors. Analysis was by intention to treat.
Decreasing age, improved performance status, higher body mass index, node-positive status, P16-negative status, and oral cavity primary predicted a higher ω ratio. Patients with ω score ≥0.80 were more likely to benefit from intensive treatment [5-year overall survival (OS), 70.0% vs. 56.6%; HR of 0.73, 95% confidence interval (CI): 0.57-0.94; = 0.016] than those with ω score <0.80 (5-year OS, 46.7% vs. 45.3%; HR of 1.02, 95% CI: 0.92-1.14; = 0.69; = 0.019 for interaction). In contrast, the effectiveness of intensive therapy did not depend on risk of progression.
Patients with HNC with a higher ω score selectively benefit from intensive treatment. A nomogram was developed to help select patients for intensive therapy.
先前的研究表明,治疗的获益取决于患者癌症复发相对于非癌症死亡的风险(ω 比)。我们旨在检验以下假设,即具有更高 ω 比的头颈部癌症(HNC)患者选择性地从强化治疗中获益。
我们分析了在三项 III 期试验(RTOG 9003、RTOG 0129 和 RTOG 0522)中接受原发放疗(RT)联合或不联合全身治疗的 2688 例 III-IVB 期 HNC 患者。我们使用广义竞争事件回归根据 ω 比对患者进行分层,并根据预测的 ω 比(即 ω 评分)比较强化治疗的效果。强化治疗定义为在具有改变分割和/或多药物同期全身治疗的实验组中进行的治疗。开发了一个列线图,根据肿瘤、人口统计学和健康因素预测患者的 ω 评分。分析采用意向治疗。
年龄降低、体能状态改善、体重指数增加、淋巴结阳性状态、P16 阴性状态和口腔原发肿瘤与更高的 ω 比相关。ω 评分≥0.80 的患者更有可能从强化治疗中获益[5 年总生存率(OS):70.0% vs. 56.6%;HR:0.73,95%置信区间(CI):0.57-0.94;P=0.016],而 ω 评分<0.80 的患者获益较少[5 年 OS:46.7% vs. 45.3%;HR:1.02,95% CI:0.92-1.14;P=0.69;P=0.019 用于交互作用]。相反,强化治疗的效果并不取决于进展风险。
具有更高 ω 比的 HNC 患者选择性地从强化治疗中获益。开发了一个列线图来帮助选择接受强化治疗的患者。